scholarly journals Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Deborah M. Stephens ◽  
Ken Boucher ◽  
Elizabeth Kander ◽  
Sameer A. Parikh ◽  
Erin M. Parry ◽  
...  

Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin Transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age at HT was 67 years (range, 38-85). Median time from CLL diagnosis to HT was 5.5 years (range, 0-20.2). Prior to HT, patients received a median of 2 therapies for CLL (range, 0-12). As initial therapy for HT, 61% (n=62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine). Seven (7%) patients received hematopoietic cell transplantation (HCT) while in first complete remission (CR1). The median number of treatments for HT per patient was 1 (range, 0-5) with 59 (61%) patients only receiving one line of therapy. After HT, patients had a median follow-up of 1.6 years (range, 0-15.1). Two-year overall survival (OS) after HT diagnosis was 72% (95%CI 62-83%). The patients who received standard ABVD-based therapy had a median OS of 13.2 years. Although limited by small sample size, the patients who underwent HCT for HT in CR1 had a similar 2-year OS (n=7; 67%) compared to patients who did not undergo HCT for HT in CR1 (n=87; 72%; p=0.46). In this multi-center study, HT patients treated with ABVD-based regimens had prolonged survival supporting the use of these regimens as standard of care for these patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4385-4385
Author(s):  
Mariangela Mura ◽  
Alessandra Trojani ◽  
Silvia Soriani ◽  
Alessandra Tedeschi ◽  
Milena Lodola ◽  
...  

Abstract Abstract 4385 Introduction Conventional cytogenetic and FISH studies with the standard panel (13q14, 11q22.3, 17p13, 12, 6q23) are used to detect chromosomal abnormalities of clinical significance in patients with chronic lymphocytic leukemia (B-CLL). Recently, translocations and 5'IGH deletions involving chromosome14q32 are associated with B-CLL. Aim Our aim was to investigate the presence and the characteristics of chromosome 14q32 aberrations in a group of patients with B-CLL. Patients and Methods A total of 58 patients with B-CLL were investigated by conventional cytogenetic, in addition the cultures were stimulated with CpG oligodeoxynucleotide plus IL2. FISH studies with 14q32/IGH break-apart probe designed to detect chromosomal breakage of the IGH (14q32) locus, were done for 59 patients. Results Chromosomal abnormalities were detected in 60.3% of cases by cytogenetic. 14 patients showed complex cariotype while trisomy 12 was the most frequent anomaly found in 8 patients. Among the twelve other patients several chromosomal aberrations were noted: del(13)(q14), del(13)(q12q21), del(13)(q12q14), del(13)(q13q32), +21, t(11;13)(q23;q14), +12 t(1;4)(q31;p14), t(3;14)(p21;q22), del (11)(q12) +21, del(6)(q21), inv3(?p13q21), del(11)(q12). Abnormalities of chromosome 14 were found in 23.8% of patients. Deletion of 5'IGH, corresponding to the variable IGH segment, was the most frequent anomaly found in 8 patients. Interesting, a 3'IGH deletion was detected in two patients, while only one patient showed a complete deletion of chromosome 14 (47,XXY,add14q32). Three patients showed 14q32 translocations involving the IGH locus. Conclusions Based on our findings, deletions of the variable region of the IGH gene (IGHv) and 14q32/IGH translocations are involved in B-CLL. As these preliminary data are based on small sample size, our goal will be to study the cytogenetic profile of a large number of CLL patients. Future studies will permit the identification of 14q32 translocations and the type and the frequency of IGH rearrangements. Finally, chromosome 14 abnormalities will be correlated to other cytogenetic and FISH abnormalities, and associations with known prognostic markers, such as IGVH mutation status and ZAP-70 expression, will be investigated. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Leticia R. Cruz ◽  
Idania Baladron ◽  
Aliusha Rittoles ◽  
Pablo A. Diaz ◽  
Carmen Valenzuela ◽  
...  

Purpose: The instrumental role of CK2 in the SARS-Cov2 infection has pointed out this protein kinase as a promising therapeutic target in Covid-19. Anti-SARS-Cov2 activity has been reported by CK2 inhibitors in vitro; however, any anti-CK2 clinical approach has been investigated in Covid-19. This exploratory trial aimed to explore safety and putative clinical benefit of CIGB-325, an anti-CK2 peptide previously assessed in cancer. Methods: A monocentric, parallel group design, therapeutic exploratory trial of intravenous CIGB-325 in adults hospitalized with Covid-19 was performed. Twenty patients were randomly assigned to receive CIGB-325 (2.5 mg/kg/day during 5-consecutive days) plus standard-of-care (10 patients) or standard-of-care (10 patients). Adverse events were classified by the WHO Adverse Reaction Terminology. Parametric and non-parametric statistical analyses were performed according to the type of variable. Considering the small sample size, differences between groups were estimated by Bayesian analysis. Findings: CIGB-325 induced transient mild and/or moderate adverse events like pruritus, flushing and rash in some patients. Both therapeutic regimens were similar respect to SARS-Cov2 clearance in nasopharynx swabs over the time. However, CIGB-325 significantly reduced the median number of pulmonary lesions (9.5 to 5.5, p = 0.042) at day 7 and proportion of patients with such effect was also higher according to Bayesian analysis (pDif > 0; 0.951). Additionally, CIGB-325 significantly reduced the CPK (p = 0.007) and LDH (p = 0.028) plasma levels at day 7. Implications: Our preliminary findings suggest that this anti-CK2 clinical approach could be combined with standard-of-care in Covid-19 thus warranting larger studies.


2020 ◽  
Author(s):  
Sean Horoho ◽  
Stephen Musik ◽  
David Bryant ◽  
William Brooks ◽  
Ian M Porter

ABSTRACT It is well established that coronavirus disease 2019 is primarily transmitted through respiratory droplets, and there is mounting research speculation that it may also be transmitted via fomites. Several studies have shown that the virus can persist on both porous and nonporous surfaces for hours to days, depending upon the material. This article examines three cases of polymerase chain reaction–proven severe acute respiratory syndrome coronavirus 2 infection with several additional individuals meeting CDC close contact criteria. In 1 case, 195 downstream contacts were all tested to prevent a mass outbreak in a deployment posture. Analysis of these contacts yielded only a single positive test, which could be reasonably ascribed to respiratory droplet transmission. While these cases and their contacts ultimately represent a small sample size, we suggest fomite spread may not be a significant means of transmission for severe acute respiratory syndrome coronavirus 2 in real-world operational scenarios.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18687-e18687
Author(s):  
Maya Leiva ◽  
Angela Pennisi ◽  
Kathleen Kiernan Harnden ◽  
Patricia Conrad Rizzo ◽  
Lauren Ann Mauro

e18687 Background: The long-acting injectable G-CSF, pegfilgrastim and its biosimilars have historically been given to patients 24 hours following the administration of myelosuppressive chemotherapy for either primary or secondary prophylaxis of febrile neutropenia (FN). Previous literature has indicated that pegfilgrastim administration prior to 24 hours post chemotherapy, may result in a deepened and prolonged neutropenia due to the increase in circulating granulocytes exposed to chemotherapy. With the onset of the COVID-19 pandemic and to reduce potential SAR-CoV-2 exposure to cancer patients on therapy, we implemented same day administration of injectable pegfilgrastim-cbqv among select breast cancer patients receiving myelosuppressive chemotherapy regimens from March 2020 – February 2021. Methods: Utilizing retrospective EHR chart reviews, 55 patients among 4 medical oncologists in our breast cancer group were identified as meeting the criteria of same day pegfilgrastim-cbqv administration. Inclusion was based on completion of at least 2 consecutive cycles of same day pegfilgrastim-cbqv 6 mg subcutaneous injection for primary or secondary prophylaxis. The selected patient charts were reviewed for the incidence and severity of FN. Among the patients who had documented FN, further subgroup analyses were done regarding baseline characteristics, timing of neutropenia, regimens, regimen sequence, and reported ADRs associated with pegfilgrastim-cbqv. Results: 9 (16.4%) of the 55 patients experienced FN (Grades 3-4) and 6 (10.9%) patients were hospitalized. There were no Grade 5 events and none had therapy discontinued due to FN. 8 (88.9%) of the patients experienced FN between cycles 1 and 2. Of note, there were no cases of COVID-19 among the 9 patients who had an episode of FN. 52 (94.5%) of the 55 patients received treatment with curative intent and 3 (5.5%) had metastatic disease on a subsequent line of therapy. The median age was 49.1 years (range 29-71) and patients were 56.4% Caucasian, 18.1% Black or African American, 12.7% Asian, and 12.7% Hispanic/Latina. Conclusions: Based on the retrospective data analysis, same day pegfilgrastim-cbqv appears to be a safe and effective option in the primary and secondary prophylaxis of FN with myelosuppressive standard of care chemotherapy used in breast cancer treatment. Though our review was limited by a relatively small sample size and confined to younger (49.1 median age) breast cancer patients, this opens the door to further re-evaluation of same day pegfilgrastim-cbqv administration in other patient populations. In a post pandemic treatment world, this slight change in practice has the potential to reduce patient financial toxicity associated with multiple medical visits, provide an alternative to on-body injector formulations, and ensure treatment adherence.


Author(s):  
Rujuta Katkar ◽  
Narasa Raju Madam

Objectives: This paper seeks to explore the hypothesis of the potential diabetogenic effect of SARS-COV-2 (Severe Acute respiratory syndrome coronavirus). Case series presentation: We present a case series of observation among 8 patients of age group ranging from 34 to 74 years with a BMI range of 26.61 to 53.21 Kilogram/square meters that developed new-onset diabetes after COVID-19 infection. Severe Acute Respiratory Syndrome Coronavirus (SARS-COV-2), commonly known as Coronavirus or COVID-19(Coronavirus infectious disease), gains entry into the cells by binding to the Angiotensin-converting enzyme-2(ACE-2) receptors located in essential metabolic tissues including the pancreas, adipose tissue, small intestine, and kidneys. The evidence reviewed from the scientific literature describes how ACE 2 receptors play a role in the pathogenesis of diabetes and the plausible interaction of SARS-COV-2 with ACE 2 receptors in metabolic organs and tissues. Conclusion: The 8 patients without a past medical history of diabetes admitted with COVID-19 infection developed new-onset diabetes mellitus due to plausible interaction of SARS-COV-2 with ACE 2 receptors. The resulting downregulation of ACE-2 and ACE-2 receptors expression caused islet-cell damage resulting into diabetes. The resulting observation has the potential to adversely impact significant number of the globally affected population. Screening patients with COVID-19 for diabetes routinely can help in early detection, significantly reducing morbidity and mortality associated with diabetes. Due to limitations of observational study with a small sample size will require further investigation in the form of Clinical trial.


2003 ◽  
Vol 21 (7) ◽  
pp. 1278-1284 ◽  
Author(s):  
Mark A. Weiss ◽  
Peter G. Maslak ◽  
Joseph G. Jurcic ◽  
David A. Scheinberg ◽  
Timothy B. Aliff ◽  
...  

Purpose: Purine analogs and alkylators are important agents in the treatment of chronic lymphocytic leukemia (CLL). Previously, combinations of fludarabine and chlorambucil were abandoned because of increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin may be least myelosuppressive. We hypothesized that combining pentostatin with cyclophosphamide would have less myelotoxicity than combinations using other purine analogs. Patients and Methods: We studied 23 patients with previously treated CLL. All patients received pentostatin 4 mg/m2. Seventeen patients received cyclophosphamide 600 mg/m2, and six patients received cyclophosphamide 900 mg/m2. Both drugs were administered on day 1 of each cycle, and cycles were repeated every 3 weeks for six treatments. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically. The median number of prior treatment regimens was three (range, one to five) with 13 patients (57%) refractory to prior fludarabine therapy. Results: The cyclophosphamide 900 mg/m2 dose level was associated with moderate to severe nausea, and we chose cyclophosphamide 600 mg/m2 as the dose for further study. There were 17 responses (74%; 95% confidence interval, 63% to 85%), including four complete responses. The response rate was 77% in fludarabine-refractory patients. Myelosuppression was acceptable with grade 3/4 neutropenia and thrombocytopenia, seen in 35% and 30% of patients, respectively. The relative sparing of thrombopoiesis can be seen in that only one patient (5%) with an initial platelet count of more than 20,000 required platelet transfusions while receiving therapy. Conclusion: Pentostatin 4 mg/m2 with cyclophosphamide 600 mg/m2 is safe and effective in previously treated patients with CLL. On the basis of these results, we are currently studying pentostatin, cyclophosphamide, and rituximab (PCR) therapy in patients with CLL.


Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1724-1730 ◽  
Author(s):  
Julio Delgado ◽  
Kirsty Thomson ◽  
Nigel Russell ◽  
Joanne Ewing ◽  
Wendy Stewart ◽  
...  

We report results in 41 consecutive patients with chronic lymphocytic leukemia (CLL) who underwent allogeneic hematopoietic cell transplantation (HCT) after fludarabine, melphalan, and alemtuzumab conditioning. Donors were 24 HLA-matched siblings and 17 unrelated volunteers, 4 of them mismatched with recipients. All but 3 patients had initial hematologic recovery, but 5 more patients had secondary graft failure. Median intervals to neutrophil (greater than 0.5 × 109/L) and platelet (greater than 20 × 109/L) recovery were 14 days (range, 9-30 days) and 11 days (range, 8-45 days), respectively. Eleven (27%) patients had relapses and received escalated donor lymphocyte infusions, but only 3 of them had sustained responses. Acute and chronic graft-versus-host disease (GVHD) was observed in 17 (41%) and 13 (33%) patients, respectively. Seventeen (41%) patients have died, 5 of progressive disease. The 2-year overall survival and transplantation-related mortality (TRM) rates were 51% (95% confidence interval [CI], 33%-69%) and 26% (95% CI, 14%-46%), respectively. The alemtuzumabbased regimen was feasible and effective in patients with CLL with a relatively low rate of GVHD. However, TRM remains relatively high as a result of a variety of viral and fungal infections. Studies are ongoing to address the efficacy of reduced doses of alemtuzumab in this group of immunosuppressed patients.


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